Borggrefe Tilman, Oswald Franz
Institute of Biochemistry, University of Giessen, Giessen, Germany.
Center for Internal Medicine, Department of Internal Medicine I, University Medical Center Ulm, Ulm, Germany.
PLoS Biol. 2016 Jul 26;14(7):e1002524. doi: 10.1371/journal.pbio.1002524. eCollection 2016 Jul.
Notch signaling is iteratively used throughout development to maintain stem cell potential or in other instances allow differentiation. The central transcription factor in Notch signaling is CBF-1/RBP-J, Su(H), Lag-1 (CSL)-Su(H) in Drosophila-which functions as a molecular switch between transcriptional activation and repression. Su(H) represses transcription by forming a complex with the corepressor Hairless (H). The Su(H)-repressor complex not only competes with the Notch intracellular domain (NICD) but also configures the local chromatin landscape. In this issue, Yuan and colleagues determined the structure of the Su(H)/H complex, showing that a major conformational change within Su(H) explains why the binding of NICD and H is mutually exclusive.
Notch信号通路在整个发育过程中反复被用于维持干细胞潜能,或在其他情况下促进分化。Notch信号通路中的核心转录因子是CBF-1/RBP-J、果蝇中的Su(H)、Lag-1(CSL)-Su(H),它作为转录激活和抑制之间的分子开关发挥作用。Su(H)通过与共抑制因子Hairless(H)形成复合物来抑制转录。Su(H)-共抑制因子复合物不仅与Notch细胞内结构域(NICD)竞争,还会塑造局部染色质景观。在本期杂志中,Yuan及其同事确定了Su(H)/H复合物的结构,表明Su(H)内的一个主要构象变化解释了为什么NICD和H的结合是相互排斥的。